The primary objective of this project is to investigate the basic mechanisms underlying the cause of the longterm neurodevelopmental handicap frequently observed in premature infants who have intraventricular hemorrhages. The study makes use of an innovative, powerful and non-invasive technology that has great potential for application to further investigations of neurobiological interest. This technique is nuclear magnetic resonance (NMR) which provides the only methods where information on neuroanatomy, cerebral metabolism and brain function can be obtained non-invasively using a single instrumentation system. Both detailed information about the neuroanatomy and functional anatomy of normal infants and infants with IVH will be obtained by new, unique magnetic resonance imaging methods. Data on both the acute and chronic alterations in cerebral metabolism in immature animals exposed to hypoxia and ischemia will be investigated. Measurements of the changes in the steady-state concentration of cerebral amino acids, creatine, inositol, high-energy phosphates and intracellular Ph will be made in vivo using 1H NMR methods. The overall objective will be to use these powerful, non-invasive methods to obtain a better understanding of the pathogenesis of hypoxic-ischemic encephalopathy. Another major objective will be to determine the feasibility and value of applying the more complicated and costly NMR spectroscopic techniques to further investigations in the human newborn. The metabolic and biochemical data obtained from the spectroscopic studies can then be combined in the future studies with the neuroanatomical and functional information obtained from imaging.